Association Between Volume of Fluid Resuscitation and Intubation in High-Risk Patients with Sepsis, Heart Failure, End-Stage Renal Disease, and Cirrhosis.

Study: Association Between Volume of Fluid Resuscitation and Intubation in High-Risk Patients with Sepsis, Heart Failure, End-Stage Renal Disease, and Cirrhosis. Khan et al. CHEST 2019.

Clinical question: In patients with sepsis and septic shock who have co-morbid conditions of CHF, ESRD and Cirrhosis, is the full 30 cc/kg IVF bolus associated with higher rates of intubation?

Methods:

Single center, retrospective study

Included patients with CHF (HFrEF, HFpEF), ESRD and Cirrhosis

Sepsis identified through APACHE database, ICD9 and 10 codes followed by trained clinician review based on a published clinical sepsis surveillance definition

Calculated IVF given as bolus fluids in the first 6 hours of hospital arrival; did not include maintenance fluids given in first 6 hours, also did not include fluids given by EMS personnel prior to hospitalization

Primary outcome: Intubation within 72 hours from fluid bolus

Secondary outcomes:

-          Time to intubation

-          Change in oxygen requirement

-          Alive ICU free days

-          Ventilator days

-          Hospital mortality

Included patients assigned to 1 of 2 cohorts:

-          > 30 cc/kg IVF (standard group)

-          < 30 cc/kg IVF (restricted group)

Results:

286 patients included, 208 matched patients (104 standard resuscitation, 104 restrictive group)

No statistical differences between patient characteristics and clinical variables between groups except for:

-          Fluid volume in first 6 hours 1.39 +/- 700 L (restricted) vs 3.38 +/- 1.06 L (standard) (p < 0.001)

-          Fluid volume in first 24 hours 2.38 +/- 1.35 L vs 4.38 +/- 1.61 L (p < 0.01)

-          Fluid balance at 72 hours approached a significant difference 3.17 L vs 4.20 L (p = 0.054)

-          DNI status 3% (restricted) vs 11% (standard)

Notably, there were no differences in vasopressor or diuretic use in the first 72 hours or differences in rates of non-invasive ventilation.

There were no differences in the primary or secondary study outcomes:

After adjustment for APACHE III score, lactate level, steroid use, change in oxygen requirement from baseline, noninvasive ventilation use, fluid balance at 72 h, DNI status, and presence of CHF, cirrhosis, or ESRD with multivariable generalized estimating equation, administration of > 30 mL/kg fluid resuscitation (standard resuscitation) was not independently associated with intubation (P = .34).

Strengths:

-          This trial asks an important question. Early and aggressive IVF resuscitation is a mainstay in the treatment of patients with sepsis and septic shock and is recommended by the Surviving Sepsis Campaign. Clinicians often site the presence of the co-morbid conditions studied in this paper as justification to not order the recommended 30 cc/kg IVF bolus.

-          The findings in this paper correspond with two prior publications which come to mind suggesting the optimal dosing of IVF for patients sepsis patients is around 30 cc/kg IVF:

o    Liu et al. Ann Am Thorac Soc Vol 10, No 5, pp 466–473, Oct 2013 , demonstrates a “J-Shaped” curve for IVF administration and mortality with inflection points occurring at < 7.5 cc/kg and > 45 cc/kg.

-          Leisman et al. Crit Care Med 2018; 46:189–198 demonstrated that > 50% of patients with CHF and ESRD were “fluid responsive” to an initial fluid bolus in the ER.

Weaknesses:

-          Retrospective study. Can not determine causation.

-          Relatively small number of patients, wide confidence interval for intubation in 72 hours (C.I. = 0.41-1.36)

-          Did not risk stratify patients within disease categories, for example, patients with EF 5% vs 40%

-          Did not include maintenance fluid volume or fluid given by EMS personnel

-          Does not offer explanation as to why some patients received full 30 cc/kg IVF bolus while others did not

Conclusion: The 30 cc/kg IVF bolus recommended by the Surviving Sepsis Campaign does not appear to be associated with higher rates of intubation in high risk patients with sepsis. The presence of co-morbid conditions such as CHF, ESRD and Cirrhosis alone should not dissuade clinicians from ordering the full dose bolus. Clinicians should continue to use additional data points such as point of care ultrasound, laboratory and hemodynamic markers of perfusion to aid in decision making. 

-by John Kazianis, MD , Medical Director AICU